Caloric restriction (CR: reducing caloric intake 30-40 percent below ad libitum levels) remains the only intervention that reproducibly extends lifespan, reduces the incidence and delays the onset of age-related disease, enhances stress protection, and attenuates functional decline in mammals. The NIA longitudinal study of CR and aging in rhesus monkeys finished its 21st year. Monkeys continue to be monitored regularly. Previous work tested the overall T-cell function and existing memory/persistent immune response maintained during aging. In a follow up experiment, we evaluated the ability of naive T-cells to mount a new immune response to an antigen that the monkeys have not been exposed to previously. This is important because of the generally weak response of elderly humans to vaccinations and may resolve whether it is naive, not memory responses that are preferentially affected in aging. An initial immunization was followed by blood collections and two booster immunizations over the course of approximately four months. Blood samples are currently being analyzed. A study of ligature-induced inflammation in the oral cavity was completed in a subset of monkeys. Local and systemic measures of immune function were evaluated for 90 days and compared to the controls, CR monkeys had a significantly lower gingival index, less bleeding on probe, less probing depth and calculus. Additionally, periodontal destruction progressed more slowly in the CR monkeys. These findings are consistent with an anti-inflammatory effect of CR and indicative of a protective effect. Monkeys continue on a regular rotation to receive eye exams and fundus photographs. Females had a higher prevalence and severity of drusenoid maculopathy than males;this gender difference is not consistently found in humans. To date, no effect of CR has been identified. A major research focus for the aging monkeys continues to be behavior changes. Locomotor testing is evaluated every three years and preliminary results indicate that CR monkeys tend to be more active than controls during the day but less active at night. Complex tasks of learning and memory using custom-made portable touch-screen panels are currently underway. Motor performance was assessed using an automated monkey Movement Assessment Panel (mMAP) that has reproducibly and reliably measured reaction time, coarse-motor, and fine-motor movement in rhesus monkeys and humans. In our study, an age-related decline in fine motor performance has been observed that was partially ameliorated in the CR monkeys. We continue to monitor morbidity and mortality.